Bile Salt Hydrolase Amino Transfer to Bile Acids
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ABSTRACT:
PROVIDER: PRJEB67375 | ENA |
REPOSITORIES: ENA
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Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA in shock experiments as well as during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection.
2019-02-12 | PXD010514 | Pride
Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection
2019-02-09 | PXD010525 | Pride
Project description:Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1-6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.
| S-EPMC10881385 | biostudies-literature
Project description:Clostridium difficile epidemic strain R20291 was grown in presence of the two main bile acids, Deoxycholate and Cholate.
2019-08-28 | GSE86152 | GEO
Project description:Bile acids from 88 different species of animals collected by Lee Hagey and others
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Project description:The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-b-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.
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Project description:Bifidobacterium are considered to be beneficial for human health and are classified as probiotic bacterium. They must resist many environmental stress factors in order to survive in the gastrointestinal environment including; pH, oxygen availability, bile and nutrient starvation (eg: iron or carbon). This study investigates Bifidobacterium breve UCC2003 global genome response to growth under ferrous and/or ferric iron limiting conditions. Revealing that growth under iron limitation effects many processes in the cell including carbon and nitrogen metabolism and induces/reduces the expression of numerous genes; including multiple iron uptake systems, DPS proteins (which are predicted to be involved in iron storage/DNA protection), Fe-S cluster associated proteins and a bile salt hydrolase (bshB). Insertional mutagenesis and survival assays were employed and demonstrated that iron starvation imposed on B. breve UCC2003 results in an increased resistance to bile stress due to in part the iron-inducible transcription of the bshB gene. Furthermore, this study links BSH activity in B. breve UCC2003 to its ability to survive the deleterious effects of bile salt and suggest that B. breve UCC2003 may be use iron as a signal to adapt to the constantly changing environment within the small intestine.
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Project description:Bile acids are not only crucial for the uptake of lipids, but also have widespread systematic ef-fects and shape the gut-microbiome composition. Bile acids can directly shape the gut-microbiome and can be modified by bacteria such as Eggerthella lenta which in turn plays a crucial role in host metabolism and immune response. We cultivated eight strains that represent a simplified human intestinal microbiome and inves-tigated the molecular response to bile acids, co-culturing with Eggerthella lenta and the combina-tion. We observed growth inhibition of particularly gram-positive strains during bile acid stress, which could be alleviated through co-culturing with Eggerthella lenta. The inhibition of growth was related to a decrease in membrane integrity and genotoxic effects of bile acids, which we investigated using zeta potential measurements in combination with proteomic and metabolomic analyses. Co-culturing with Eggerthella lenta alleviated stress through formation of oxidized and epimer-ized bile acids and the molecular response to co-culturing was seen to be strain specific. We also note that we could detect the recently described Microbial Bile Salt Conjugates in our cultures. This study highlights the significance of a potent bile acid modifier and how in-depth molecular analyses are required to decipher cross-communication between gut and host.
2023-02-24 | PXD035496 | Pride
Project description:The effects of bile acids on human placental proteome was examined
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